Atmospheric Pressure Ion (API) Sources configured with Electrospray (ES) ionization interfaced to mass analyzers include at least one Electrospray sample introduction probe. Commercially available ES probes can be roughly categorized into two types, flow-through and non flow-through configurations. The non flow-through ES probes are usually configured as pre-loaded microtips where no additional sample solution is added during the spraying process. Flow-through ES probes allow the delivery of a continuous solution flow to the ES probe tip from a fluid delivery system located outside the ES chamber. ES flow-through tips have been constructed with one or more straight tube layers to simultaneously deliver liquid and gas from the attached transfer lines to the ES probe tip during operation. Flow-through ES probes are typically configured with flexible solution and gas transfer lines connected to a probe body. The liquid and gas transfer lines may be attached to the ES probes at various angles, but the single or layered tubes within ES probes have been configured as straight tubes from the point of delivery line attachment to the ES probe tip. Even in ES probes configured with a single tube for liquid sample delivery, the single tube within the ES probe body is straight after the liquid transfer line attachment point to the ES probe body. When a single layer ES probe configuration is used, the sample bearing liquid is Electrosprayed directly from the exit tip of the probe tube. When it is desirable to operate Electrospray with pneumatic nebulization assist, a second layer tube is positioned surrounding and concentric to the innermost solution introduction tube, through which nebulization gas is delivered to the ES probe tip. Three concentric tube layers have been configured in ES probes to deliver a second liquid flow layered over the sample solution with a third layer for introduction of nebulizing gas at the ES probe tip.
Electrospray probes with straight single or layered tube configurations have been positioned on or off axis in Electrospray ion sources. Electrospray probes have been mounted with the probe tip axis aligned with the ES source axis as defined by the axis of the orifice into vacuum. ES probe assemblies have been configured in a fixed on-axis position or with the ability to have the probe tip position rotated and translated in the x, y and z direction around the ES source centerline. Off-axis ES probe assemblies have also been configured where the probe straight tube axis is generally positioned to direct the Electrosprayed solution toward the ES source centerline near the centerline of the orifice into vacuum. Off axis ES probes which incorporate pneumatic nebulization assist have also been used for higher liquid flow rate applications, as is described in U.S. Pat. No. 5,495,108. An off-axis Electrospray probe configured with pneumatic nebulization assist is generally mounted at an angle ranging from xcfx86=40xc2x0 to xcfx86=90xc2x0 relative to the ES source vacuum orifice centerline. U.S. Pat. No. 5,495,108 even describes that an ES probe with pneumatic nebulization assist can be mounted in a position xcfx86=180xc2x0 relative to the direction of gas flow through the vacuum orifice leading to the mass spectrometer. Analytica of Branford, Inc. has also configured ES sources with single or multiple ES probes mounted in a single source (see, Analytica""s PCT patent application entitled Multiple Sample Introduction Mass Spectrometry and filed Sep. 11, 1998). In all cases, each ES probe assembly individually was configured with a straight and concentric single or layered tube assembly after the transfer line attachment points.
The straight ES probe assembly configuration requires that the entire ES probe body be angled and positioned to achieve the optimal ES probe tip position in an ES source chamber. This configuration of straight tube ES probes imposes constraints on the ES source chamber design, particularly for xe2x80x9coff-axisxe2x80x9d ES probetip orientation. When off-axis ES probe mounting is used, the ES source chamber must be configured large enough to fit the ES probe body and transfer line attachments within the ES source chamber. Alternatively, the ES probe length must be increased or the ES chamber size reduced if it is desirable to position the off-axis ES probe body outside the ES source chamber with the probe assembly extending through the side wall of the ES chamber. When ES source configurations require applying kilovolt potentials to ES probes during operation, appropriate electrical insulation must be applied to any ES probes extending through the ES chamber walls. In some ES source configurations, ES probes are operated at ground potential, and kilovolt potentials are applied to surrounding electrodes. ES probes which extend through these electrodes can pass close to these electrodes and must be appropriately insulated. The surrounding electrode shapes and ES probes must be configured to accommodate xe2x80x9con-axisxe2x80x9d and xe2x80x9coff-axisxe2x80x9d ES probe position placement while producing the desired electric fields during operation, even over a wide range of liquid flow rates.
An ES source can accommodate a sample liquid flow rate range of over 10,000 to 1. Depending on the analytical application, sample liquid can be sprayed at flow rates ranging from less than 25 nanoliters per minute to over 2.5 milliliters per minute. To achieve optimal performance over this range of liquid flow rates, ES sources can be configured to accommodate a number of ES probe configurations and a range of ES probe positions. For lower liquid flow rate applications, ES probes are generally positioned on or near the ES source centerline. With higher flow rate applications, ES probes may be positioned off the ES source centerline angled toward the centerline to optimize ES performance. To achieved added flexibility in operation, more than one ES probe can be mounted in the ES source simultaneously and even operated simultaneously. The size, complexity and cost of an ES source increases when it must accommodate the mounting of one or more ES probes in multiple positions when the ES probes are configured with straight single or multiple liquid and gas tubes after the transfer line attachment point. Particularly in low liquid flow rate applications where it is important to minimize dead volume, the liquid transfer lines are typically mounted xe2x80x9cin-linexe2x80x9d with the ES probe liquid sample delivery tube. The xe2x80x9cin-linexe2x80x9d connection of the sample delivery tube with the ES probe tube assembly may increase the ES probe length placing additional size and position constraints on the ES source and probe design.
In accordance with the present invention, the reconfiguration of ES probe delivery tubes is provided in a curved manner which relieves several of the design and operational constraints imposed by straight ES probe configurations. The curved or bent ES probe configuration increases the versatility of ES probe placement and operation and allows cost effective ES source design with little compromise in performance.
The present invention incorporates a curved tube configuration into ES probe assemblies. The curved tube ES probe configuration enables independent positioning of the ES probe tip and the probe body within an ES source chamber. This curved shape incorporated into ES probe assemblies allows single and multiple ES probe mounting positions to be achieved with simpler and lower cost ES source assemblies. In one embodiment of the invention described, a curved or bent ES probe is mounted to the back plate of an API source. This probe configuration includes concentric tubes that are bent in a double curve shape where the ES probe body is positioned with its axis along the ES source chamber centerline, and the ES probe tip is positioned off-axis and angled toward the ES source chamber centerline. Independent of the ES probe body orientation, the ES probe curve can be shaped such that the probe tip is positioned off axis pointing at an angle toward the centerline defined by the centerline of the ES source orifice into vacuum. The position of this ES probe tip, which may include layered liquid flow and/or pneumatic nebulization assist, can be adjusted in axial and angular directions relative to the vacuum orifice location to optimize ES source performance for a given application. The curved ES probe assembly can be configured to allow adjustment of the ES probe tip position during ES source operation. The ES probe position can be adjusted to fall on the vacuum orifice centerline or to a position well off the centerline. The curved probe configuration can accommodate any desired angle of spray relative to the vacuum orifice centerline. In addition, the invention enables the placement and simultaneous operation of multiple curved ES probes or combinations of straight and curved ES probes mounted in a single ES source. Different sample solutions can be introduced into the ES source chamber simultaneously through multiple ES probes during operation. To reduce cost and complexity of the ES source, all curved or combinations of curved and straight ES probes can be conveniently mounted to or through the back plate of the ES source chamber. Alternatively, combinations of back and side mounted probes can be configured in an ES source, if desired.
In one embodiment of the invention, an Electrospray ion source is configured with an Electrospray probe which includes a bent or curved portion in its fluid and gas delivery tubes. The ES probe body is mounted with its axis substantially aligned with the Electrospray source centerline and is configured with a three layer ES probe tip positioned off-axis to spray at an angle toward the ES source centerline as defined by the vacuum orifice centerline. The ES probe body includes means to adjust the probe tip position in the ES source chamber. The three layer bent or curved probe comprises liquid and gas delivery tubes that are configured with a double bend. This double bend allows the sample solution to enter the delivery tube flowing in a direction substantially aligned with the ES source centerline. The solution is sprayed toward the ES source centerline from the exit end of the delivery tube which is also the ES probe tip which is positioned off-axis. The axis of the ES tip and ES probe body axis are not aligned in the double bend ES probe configuration, allowing maximum flexibility in configuring ES source and ES probe geometries. The ES probe with a double bend delivery tube section can be configured with a single or multiple layered ES tip. Two and three layer ES curved ES probe tips can be operated with layered liquid flow or pneumatic nebulization assist. Curved ES probes may also be configured with ultrasonic nebulization assist. Each tube bore or annulus layer of a multiple tube curved ES probe may be connected to different gas or liquid delivery systems. In this manner, different samples, mixtures of samples and/or solvents can be sprayed simultaneously or individually in a variety of combinations at similar or different liquid flow rates. A calibration solution may be introduced through a tube layer and sprayed simultaneously with the sample solution to generate internal standard peaks in an ES spectrum. The liquid delivery systems include but are not limited to liquid chromatography pumps, syringe pumps, gravity feed vessels, pressurized vessels, and or aspiration feed vessels. Samples may also be introduced using auto injectors or xe2x80x9con-linexe2x80x9d separation systems such as liquid chromatography (LC) or capillary electrophoresis (CE), capillary electrophoresis chromatography (CEC) and/or manual injection valves. ES sources configured with curved or bent inlet ES probes can be interfaced to any MS or MS/MSn mass analyzer type including but not limited to, Time-Of-Flight (TOF), Quadrupole, Fourier Transform (FTMS), Ion Trap, Magnetic Sector or a Hybrid mass analyzers.
In another embodiment of the invention, a single or multiple layered tube ES probe is configured with a single bend portion in its fluid and gas delivery tubes. The axis of the ES probe tip is not aligned with the ES probe body axis when a single bend is configured in the ES probe delivery tubes. The curved ES probe exit tip assemblies comprising multiple tube layers can be configured with means to ensure that the relative layered tube concentricity at the ES tip is retained around a common ES probe tip centerline. When compared to asymmetric tube layering, concentric positioning of tubes configured at the ES probe tip can improve the Electrospray plume uniformity around the ES probe tip centerline. This results in improved consistency of performance in Electrospray operation with layered liquid flow and/or pneumatic nebulization assist. An Electrospray ion source can also be configured with multiple ES probes comprising at least one curved Electrospray probe. An ES probe configured with one or more bends can be mounted in an ES source chamber with the ES probe body axis positioned substantially along the ES source centerline as described above. Alternatively ES probe bodies can be mounted off-axis with fixed or adjustable tip locations. One or more curved ES probes can also be configured in an Atmospheric Pressure Chemical Ionization Source (APCI) source providing the means to produce ions by Electrospray or Atmospheric Pressure Chemical Ionization either simultaneously or independently in the same API source without the need to switch probe hardware. U.S. Patent Application (Analytica""s multiple probe patent application pending), describes the configuration of multiple sample introduction probes mounted in an ES or an Atmospheric Pressure Chemical Ionization (APCI) source, however, no curved ES probe configurations were included in the embodiments described.
The curved ES probe geometry allows greater flexibility and decreased complexity when configuring single or multiple sample introduction probes in an API source. Each curved ES probe in a set may be configured for operation with pneumatic or ultrasonic nebulization assist and multiple liquid and/or gas layering. Each liquid layer of each curved ES probe may be connected or switched to the same or different liquid delivery systems. Multiple ES probes configured in an API source allow the spraying of different liquid flow rates, and even completely different solutions delivered either simultaneously or sequentially into an API source without exchanging or even moving probe assemblies. Different ES MS analyses can be efficiently performed in a manual or unattended automated manner with little or no down time with multiple probe API source configurations. Individual sample mixtures which span different m/z ranges or sample types can be introduced through different ES probes to avoid cross contamination from one analysis to another. Depending on the unknown sample being analyzed, an optimal calibration solution can be chosen from another ES probe. For example, one m/z range calibration solution can be chosen which produces singly charged ES ions when analyzing singly charged compounds. Likewise, multiply charged ES generated calibration ions can be produced when analyzing compounds which form multiply charged ions in Electrospray ionization. The solution flow rate through a first ES probe can be controlled independent of the solution flow rate delivered through a second ES probe without having to reposition any probe tip location, change API source voltages or shut off gas or liquid flow to the second ES probe. Curved ES probe configurations allow tight clustering of ES probe tips if desired while leaving ES probe inlet ends conveniently spaced to facilitate connections of transfer lines and adjustment of probe tip positions. The multiply layered tube curved ES probe design allows for adjustment of relative tube exit end axial positions at the probe tip even during operation. In particular, the relative position of layered tube exit ends at the ES probe tip can be adjusted in a curved ES probe when the ES tip axis differs from the ES probe body axis. Due to this feature, multiple curved ES probes can be conveniently mounted through the back plate of an API source retaining full ES tip location and layered tube exit axial position adjustment even during ES operation. This capability facilitates setup and optimization time when conducting layered liquid flow CE, CEC or capillary column LC-MS analysis where the CE, CEC and/or LC columns are configured as the inner layer of a curved multiple layer ES probe.